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Thank You Autism Spectrum Disorders: Overview of Clinical Features and Clinical Services • The children and families who support our clinical and research activities • The Marcus Foundation • The JB Whitehead and Woodruff Foundations • The Children’s Healthcare of Atlanta Foundation Marcus Autism Center 4th Annual Summer Symposium on Autism Spectrum Disorder • The Georgia Research Alliance as well as • The National Institute of Mental Health • The National Institute of Child Health and Human Development Ami Klin, PhD Director, Marcus Autism Center, Children’s Healthcare of Atlanta GRA Eminent Scholar Professor & Chief, Division of Autism, Department of Pediatrics, Emory University School of Medicine Emory Center for Translational Social Neuroscience • The National Science Foundation • The Simons Foundation • The Autism Science Foundation • Autism Speaks • United Way Marcus Autism Center 2 Marcus Autism Center at a glance Marcus Autism Center • YAZ[V8+&.8-3+10J</ • ;C01-/,1,,)0N;9&0&10O • bZT`,+&& • PXT`*&+,/&30J8+/K0/9 • /+0)3,+ • &+ • *-1 • 8)1<9+*+1 • )&+&)0,8/0 • 0/%0,8/0 • )&+&)0000*+1J&$+,0&0 • /1*+1/,$/*0 • +1/J,*J%,,)J,**8+&1< • /,,/&+3,+/,$/* • 83,+)81/%/,$/* Excellence K K CLINICAL TRAINING RESEARCH ADVOCACY The Science of Clinical Care 3 Web of Relationships = PARTNERSHIPS Children’s Sibley Children’s Hughes Spalding Children’s Chamblee Georgia Tech Biomedical Engineering Georgia Tech “Behavioral Imaging Solutions” Georgia Tech several other projects Emblematic! Opportunities Atlanta Speech School National Black Church Initiative Georgia Pathway to Language Morehouse School of Medicine Satcher Leadership Institute GA Dep of Public Health GA Dep of Education GA Dep of Early Care & Learning Social visual engagement: infants (0 to 36 months) Emory Pediatrics GI, Neonat Emory Genetics Emory Yerkes Emory OB-GYN Emory Rollins Emory Nursing Emory Psychiatry UCSF UCLA Washington University Albert Einstein, NY Cornell Drexel Florida State University Harvard NICHD/Autism Speaks BSRC (> 20 sites) Foundation for NIH group Social vocal engagement: infants (0 to 36 months) Georgia State, Economics Georgia State, Neuroscience Funding Partners University Partners Autism Center of Excellence Treatment: infants & toddlers (12 to 14 months) NIH NSF HRSA Marcus Foundation / Woodruff/Whitehead Foundations Georgia Research Alliance Autism Speaks Autism Science Foundation Simons Foundation United Way Marcus Autism m Center 5 Behavioral Neuroscience: infant rhesus monkeys Challenges and Opportunities: %&*-,/1+,/)<&+3!3,+Q1/1*+1C )1/&+$1%)&,8/0,%&)/+ Reducing Age of Diagnosis & Improving Access to Care $ #$' ' 8' 9 •/&+&0,//,$+3,/&$&+0 •9/0,81,*0+5+81 • *-,/1+,/)<&$+,0&0+&+1/9+3,+,/)&),+$,81,* +,01,/ •*/&+*<,&1/&0 – /+&+$NU\+VX*,+1%0OA8103))),:8-1( •\`,-/&*/</-/,9&/0/,83+)<0/+,/ •&+$,&$+,0&0&+CXKZ1,YD[</0 •1/03))&+&09+1$,**8+&30 •,,**8+&1<K9&)0<01*,/ •&*8/0*+10<01*0&+-) /&$ #$' ' $ #$' ' 8' 9 $' )/.($" +-++1A ,))$A ,/(&+$A )3,+0%&-0 &8*)9), 8--,/10 &$%)9), 8--,/10 U</ Johnson & Myers, 2007; Dosreis et al., 2006; Heidgerken et al., 2005; Honigfeld et al., 2012; Shattuck et al., 2009; Mandell et al., 2005; 2009 #$0$ %%$&(.# (1 ($# .)'" V</0 8!#.4 #(!!(.!4/ $&!4" !9 W</0 X</0 Y</0 Z</0a /!$%"#(89 Marcus Autism Center 7 GENETIC LIABILITY MECHANISMS OF SOCIALIZATION 830*&0/8-101%)2,/* ,//&+9),-*+1 BEHAVIORAL SYMPTOMS No Genetic Determinism First 2 years of life No Brain Determinism Born to Socially Orient Reciprocal Social Interaction Text MH Johnson PhD JE LeDoux PhD Neuroplasticity WHITE MATTER DEVELOPMENT Jones et al. (2008). Arch Gen Psy, 65(8), 946-54; Klin et al. (2009). Nature, 459, 257-61; Jones & Klin (2009). J Am Acad of Child Psy, 48(5): 471-3; Jones & Klin (2013). Nature, 504, 427-431; Klin et al. (2014). Neurosci Biobehav Rev. H-J Park PhD 10 Research Enterprise at a glance • • • UW • ] AX • K • • H I • Strategy for Reseach Enterprise • Q Diagnosis Concept Psychopharmacology Behavioral Neuroscience Animal Models Neurobiology Genetics Marcus Autism Center 11 Translational Opportunities • High-throughput, low-cost, deployment of universal screening in the community • Early detection, early intervention, optimal outcome • Prevention or attenuation of intellectual disability in ASD 14 The next 10 years of genetics research Molecular Genetics at Emory Chris Gunter Steve Warren Mike Zwick Jen Mulle Peng Jin David Cutler Michael Gambello ACE Network Under-represented populations Marcus Autism Center Marcus Autism Center 15 Ontogeny & Neural Basis of Social Visual Engagement in Monkeys 16 Ontogeny & Neural Basis of Social Visual Engagement in Monkeys /(0&)13,+A:/+9&)) Kb9/0-/1/,**,* Kb*&+&+0,&)$/,8- Jocelyne Bachevalier, PhD Xiao Ping Hu, PhD Lisa Parr, PhD 17 In vivo diffusion MRI data showing major white matter pathways in a 2-week-old rhesus macaque. Jocelyne Longchuan Li, PhD Bachevalier, PhDMarcus Autism Center Neurodevelopmental transitions underlying eye fixation in the first 6 months of life and deviations thereof in infants and toddlers with Autism Spectrum Disorder Sarah Shultz, Longchuan Li, Xiaoping Hu, Ami Klin, Warren Jones Figure 2: Growth charts of eye fixation, 2-24 months, Typical (blue), ASD (red) Figure 1: Video Stimuli Figure 6: Example of Diffusion Tractography results, longitudinal, first 200 days of life Community-Viable Solutions: Figure 3: Differences in first 6 months of life Figure 7: Example of graph-theoretic analysis of resting-state functional brain networks from an infant Amy Wetherby, PhD Figure 8: Method to test the association between two sets of growth curves Figure 4: Hypothesis for neurodevelopmental transition underlying eye fixation Figure 8: | Functional Data Analysis and Functional Regression used to test association between 2 sets of growth curves. Data in example is from different study. A and B. Lines plots of individual trajectories of variables A and B; C and D. Smooth estimates of the trajectories in A and B; E. Association between growth curves is shown as a functional regression surface. Color scale at each point on the surface indicates the correlation coefficient, r. Regression surface indicates a significant positive association between A and B; F. Bootstrap 95% confidence intervals indicate that the relationship is significant during the period between 7.5 to 18.5 months (denoted by the red vertical bars). SOURCES - Jones & Klin (2013). Nature, 504 (7480), 427-431. - Klin, Shultz & Jones (2015). Neuroscience & Biobehavioral Reviews, 50, 189-203. - NIMH grants P50-MH100029 and R21 MH105816 8$*+3+$001, /)</1*+19&/1+/0%&-0 Primary Care Physician Family Navigator for Early Intervention Providers • Navigator for Primary Care Physicians • Navigator for Families • Parent Engagement, Clinical Trials • Community Viable Treatments, Clinical Trials • Efficacy of Early Screening & Early Intervention Jennifer Stapel-Wax, PsyD United Way Partnerships Figure 2: | Growth charts of eye fixation for typically developing (TD, blue) and ASD (red) children. Longitudinal change; between-group comparisons by functional ANOVA. Thick lines indicate mean growth curves, thin lines indicate 95% confidence intervals. Top panel is per cent fixation; middle panel change in fixation (first derivative); bottom panel plots F value functions for between-group pointwise comparisons. Significant differences are shaded in medium grey for comparison of fixation data and light grey for comparison of change-in-fixation data, with F ratio critical value marked by an arrowhead on the y axis. Figure 5: Behavior changes and hypothesized brain changes • • United Way new $ 1.875 m/3 yrs (Jennifer Stapel-Wax PI); • NIH Multi-Site R01: Marcus, Cornell, Drexel, FSU (May 2014) • Already work in Atlanta, several GA counties, as well as in FL, PA, TN and NY “Less than 20% of children with Autism in the US are identified before the age of 3 years” Marcus Autism Center 20 Treatment Research: A Paradigm Shift Treatment & neural underpinnings of food refusal • From Emory+Children’s Seed Grant to Program of Research Model System at Yerkess • Publication in high impact journal followed by NIH + Autism Speaks grant submissions • Paradigm Shift: From animal model at Yerkes to clinical trial at Marcus Shannon Gourley PhD Human Clinical Trial at Marcus Early Intervention Provider Larry Scahill, MSN, PhD Will Sharp, PhD • First Randomized Controlled Trial of a manualized behavioral intervention for feedign disorder • First investigation of a pharmacotherapy adjunct (Dcycloserine) for treatment of severe food aversion • First study of neural mechanisms underlying treatment of severe food aversion. Marcus Autism Center 22 Brief & Selective Overview of Autism Spectrum Disorders Autism is ... in 1943 as in 2014 Leo Kanner 1894-1981 Autism is ... Autism Spectrum Disorders TEST Evolutionarily Highly Conserved and Developmentally Early Emerging Mechanisms of Socialization Normative social development: Infants come into the world “pre-wired” for social engagement • From the first days of life infants are profoundly sociable • Human face and human voice are the most interesting stimuli in the environment • Early emergence of • selective attention • selective engagement • social reciprocity • attachments • social-communication skills • joint attention and social referencing skills • “Theory of Mind” • relationships 830*C +)&(&+1<-&)9),-*+1A -/&0-,0&3,+0 1, ,/&+1 1,A + +$$ :&1% -,-) / 0+1 ,/ &*-&/D Developmental Trajectories Developing expertise about the Social World Developing expertise about the Physical World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• C1%&+1+$&)0A1%8+01/818/A1%+,9)A1%&*-)&&1A 1%&+18&39A1%H,**,+0+0IA1%*+1)&03 • C1%&+,/*)A1%,+9/03,+)A1% /&-/,)A1%F,1%/K&/1GA1%-,)&1A1%F8+1/8GA1%F%5<G • C$/,,*&+$+0)K/A,*03%,/0AF08/9&9) 0(&))0GA)&9&+$&+1%,**8+&1<A8+3,+&+$&+8/8/&0A$/,8-0+ /)3,+0%&-0A)$),+/+0 • C/-3390%8)0AF1,,G)&010A-)++&+$ %A)/+&+$,/*(A'803+$1,9/&+10,0&183,+0A /,$+&=&+$+,9)1<A(+,:&+$:%++%,:1,0(00&01+A/(&+$ ,:+&$10(0&+1,01-:&0-)+0 •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ocial Attribution Task: narrative samples Typically Developing Adolescent boy, age 13-9, FSIQ = 112 *(((#,,# # !%' "%!## # %'' ! ( !'!' ( !*#)!+&*#%&)((( Klin (2000). J Child Psychol Psych Social Attribution Task: narrative samples Adolescent boy with autism, age 14-9, FSIQ = 115 %&+(&+$,811%&+$0+ 1%&+(&+$,81-,-) * #(# ( #!( !(# ( # $#( #! #(%#!' % !(% ( !, ", (((+ /%&+$,/,&)+&+$ &+)K)&&183,+0 W\</,)8)1:&1%830*N+,/*39 O M 1/10:%+0*)).8&)1/) 1/&+$)/(0,81,0.8/D 0*))0-%/,/&/)--/0 +0)&0,:+1%/,(+ /1+$)D%1/&+$)0:/ &1%/.8&)1/),/&0,0)0D 1/1%0*))A 1%&+(A&0,0)0 1/&+$)+0-%/,8+ /,8+%,1%/A*< 80,*$+3!)E Klin & Jones (2006). Brain & Cognition W\</,)8)1:&1%830*N+,/*39 O M 1/10:%+0*)).8&)1/) 1/&+$)/(0,81,0.8/D 0*))0-%/,/&/)--/0 +0)&0,:+1%/,(+ /1+$)D%1/&+$)0:/ &1%/.8&)1/),/&0,0)0D 1/1%0*))A 1%&+(A&0,0)0 1/&+$)+0-%/,8+ /,8+%,1%/A*< 80,*$+3!)E Klin & Jones (2006). Brain & Cognition • %/,(1&0&+$)8+%+ &0&+-/)&*&+/<,/&1/,8+1% /1%A:&+&+$/,8+1%*,,+ 11%--/,-/&1&01+0, 1%11%01))&1+/)0D %01))&1:0)8+%/,* 1%/,(1A+&118))<)+ ,+1%*,,+D%01))&1:0 18))<*,/)&()8+/*,8) ED Klin & Jones (2006). Brain & Cognition ,,(&+$1,-) +1/3+$ ,,(&+$1,-) ,)0+10Q8)10 ( ''$ ! ' ! (1 1+&+$%&+-/0,+G0<0 ,80,+*,81%090,80,+<0 0&0 (.)'" 1% !!1/!$% # 0& Klin et al. (2002). Arch Gen Psychiat /&+$1%%-,,&)/&+$) Klin et al. (2002). Am J Psychiat Following Social Attention Cues Following Social Attention Cues Klin et al. (2002). Am J Psychiat Following Social Attention Cues Following Social Attention Cues ,80,+1% ,+K-(/C ,+1;18)801%1 *<)1/1%*+&+$ ,0,&)0+ Klin et al. (2002). Am J Psychiat %/*&+-/&+&-)0,0,&)+ ,**8+&3,+0(&))0)/+&+$ M :/+00,,+9+3,+)/8)0,0,&) +$$*+1+0,&),+9/03,+ M 39+--/,-/&1F/&+$G,0,&) 80 M )K*,+&1,/&+$+'801*+1&+ ,+9/03,+ Active ‘reading’ of social cues • • • • • • Important for adjusting, predicting, ‘regrouping’ Eye contact / gaze Facial and bodily gestures / posture Prosodic cues (volume, inflection, rate) ‘Integrative’ cues Practice in concrete situations (rehearsals, roletaking) • Different settings – going from small therapeutic to larger naturalistic (back and forth) :/+00,,+9+3,+)/8)0 • Topic selection • Ways of marking topics shifts • Background information (presupposition and familiarity) • Knowledge base of potential conversational partners • Repertoire of interests that can be discussed • Conversational expectations (turn-taking, listening, building on what is said) • Pertinence, ‘quantity’, … (rules of pragmatics) Self-monitoring in conversation: Adjustments • Style/register (e.g., more or less formal) • Volume (e.g., in terms of social setting, proximity, number of people, and background noise) • Inflection modulation • Rate, rhythm, and stress (e.g., emphasis, affective communication) • Awareness of self style • The utilization of feedback (provided by others) %1,0&11(1,8+/01+0,&)0&183,+@ / )&+ )&+ )&+ /3++ %,/<,&+C,$+&3,+ &,'( &! //& '#3 %,/<,&+C,$+&3,+ ( 733 %,/<,&+C 1 !7$/5 What does it take to understand a social situation? OR HOW TO BUILD A SOCIAL SKILLS TRAINING CURRICULUM %,/<,&+C 1 5 !$.'5 +//&+$,&),+1;1C ( '$'(."$#('(5(0$ &!'&".'($(& $#+&(!!$( +#)$#5 Core Challenges aka Realities • SOCIAL SKILLS: the intangibles, the unstructured, the novel, the implicit, the intuitive, the “common sense”, the mentalistic • COMMUNICATION SKILLS: the informal, the conversational, the reciprocal, the ‘other-directed’, the polite, the ‘untrue’, the ‘chatty’ • ADAPTIVE SKILLS: grooming and self-care, domestic chores, ‘survival skills’, living in the community, functioning in bureaucracies, groups g p and relationships, p , legal g concerns • LEARNING SKILLS: rote & sequential, not conceptual & integrative; learning ABOUT not learning HOW TO • ORGANIZATIONAL SKILLS: repetitive schedules, ‘to do’ lists, planning ahead, learning form feedback, adjusting to variants of situations, recognizing novelty, knowing when and how to seek assistance, breaking down big tasks into stepwise plans • OBSTACLES TO ADAPTATION: anxiety, panic, fears and phobias, depression and despondency, motivational issues, rigidities ,&)/&+&/8&1/< *,/& /+1-/0,+@ ,/1D%8)1=A%DD *,/& /+1/0,+ %+8/,+1,*<, /,$+&3,+C1%80&,/*$</80 *,/& /+1'1 '#$.' $&")/)$#$' %8)1=A81%&/A)&+A1)DNVTTTOD"%%A:;AWWUKWXTD Autism Spectrum Males (n = 20) Normal Controls Males (n = 20) Right Left t maps of mean % signal change, p < .01 Masked for face-baseline & object-baseline at .05 & /+0&+'1H)&+<IL ))&+$&+),9:&1%&$&*,+ &(& #(&'(6+#)$#($ "$#(#$%! Red/Yellow Blue/Purple Right Left -Fusiform activation for Digimon characters -Amygdala activation for Digimon characters -Atypical specialization of ‘FFA’ -Emotional involvement and investment in circumscribed interests H&$&*,+IN&$&1),+01/0O Grelotti et al., 2005, Neuropsychologia Exceptional drawing ability Exceptional drawing ability <-&)\</,)&C/,8+$X,/Y <-&)\</,)&C/,8+$X,/Y 87 Exceptional drawing ability 88 However 1-%+&)10%&/%5-CJJ:::D01-%+:&)10%&/D,D8(J 89 90 Learning about autism from exceptional abilities Learning about autism from exceptional abilities 91 92 Learning about autism from exceptional abilities TEST 93 95 97 98 Learning Style M/+&+$1%:,/)A+,1+00/&)< )/+&+$%,:1,8+3,+&+1%:,/) M/101,:%,)0L8+,/18+1)<A1%:,/)&0 :%,)01,-/10 M,1+00,&39B8+,/18+1)<)/+&+$ +01,&+1$/39+,+-18) 99 101 102 103 104 ,*;*-)0 &/8*0/&&+1/010 M /.8+1+%&$%)<9&0&)*+&013,+,1%,+&3,+ M ,+,-,)&=0)/+&+$ M ,+,-,)&=01%&+(&+$ M ,+,-,)&=0,+9/03,++/)3,+0%&-0 ,1+3),/ 101/,-%&,+0.8+0 M ?? +1/010+/-339%9&,/0$18$%1 1,$1%/ND$DA1,8%&+$A0%,0A30%O M ?? +1/+1A0,)&1/<+8+*,+&1,/80, ,*-81/A-,/+,$/-%<,+1%: M %+$/,80,*&+3,+,,*-81/1%+&)0(&))0+ +&91<a)(,01/10*/10*<)1,-/,)*0:&1%1% ): M ,1-,1+3)9&3*&=/0A811%):,#+,0+,1*( 1%1&03+3,+N*+1,/<0+1+0O M ,+0+(0 M /&3+$0,&+//1 -,-) M +1%+<&+$ M )&$&,+ M 8)KK00 M -K1K/</0 M %(0-/G0-)<0 M )-%,+-,)&+08)1,/0 • • • • • • • • • ,(*,+ &$&*,+ 1%/ J/&,013,+0 )1/&)+0 %,1,$/-%&+$-,-) ,*-81/0/&)+8*/0 /$+8*/0 )$/&.83,+0 *-,/1+,/)K +31< +)K01* • Circumscribed interest may be important pillar of self-identity • Very important to take this very seriously • Examples: – Cul de sacs – Gaining insight into people through mathematics (e.g., algebraic equations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rom Early Childhood Autism, to Pervasive Developmental Disorders, to Autism Spectrum Disorders: Kanner & DSM ology M ,&))<)00*+&+$ M .8&+1+:&1%08--,/1,))$,/:,/(/0,8/0 ND$DA',,%0A1/+0&3,+$+&0A-/+108--,/1 +1:,/(0OD Marcus Autism Center 114 )&30+!+&3,+0CK AKYA+<,+ • The importance of diagnostic labels • The limitations of diagnostic labels • The political science of nosology, and the scientific politics of nosology: important considerations • The concept of reliability • The concept of validity • Nosology: expecting too much • The consequences of shifts in definitions: DSM-III, DSM-III-R, DSM-IV, and DSM-V KY:,/($/,8-/0,+&+$ – ASD vs ‘neurotypicality’ or non-ASD conditions valid – Subtyping not reliable; better mediators: severity, language level or intelligence – Best ASD + associated features • 3 domains become 2 Social/Communication are inseparable Language delays not specific to ASD: mediator Better psychometric properties (better specificity; same sensitivity) Examples across ages and levels of severity M &1%,81&+1))18)&0&)&30 L 0-/$/G0&0,// M ):<0&+1))18)&0&)&30 L 5G0&0,// L %&)%,,&0&+1$/39&0,// • Repetitive behaviors/narrow or fixated interests – – – – Requiring 2 symptoms: improves specificity Multiple sources of information History thereof improves stability of diagnosis Unusual sensory sensitivities included – Present from infancy or early childhood but more likely to be detected upon social demands • Indices of severity – – – – – – Multiple criteria in DSM-IV, same symptom – Data analyses (research on criteria) - SSC large sample • DSM-5 vs. DSM-IV-TR – 56 Studies published so far focused on DSM-5 (by 2013) – ~ 10 studies comparing Se & Sp of DSM-5 relative to DSM-IV DSM-5 definition of ASD ? (future, more quantitative) Current instruments (ADOS, ADI) Current parent reports/screeners (SRS) Current measurements of ability (Vineland) “Biomarkers” DSM-5 definition of ASD Social-Communication Restricted, Repetitive Behaviors • Persistent deficits in social communication and social interaction across multiple contexts, currently or by history: (all 3) • R e s t r i c t e d , r e p e t i t i v e p a t t e r n s o f b e h a v i o r, i n t e r e s t s or activities, current or by history: (2 of 4) – Deficits in social emotional reciprocity (from abnormal social approach and failure of back-and-forth conversation; to reduced sharing of interests, emotions; etc. ) – Deficits in nonverbal communicative behaviors used for social interaction (from poorly integrated verbal and nonverbal communication, to abnormal eye contact, etc.) to in making friends, absence of interest in peers, etc.) L 8303&0,//AK • Neurodevelopmental disorder • Smaller number of symptoms – Deficits in developing, maintaining, and understanding r e l a t i o n s h i p s (from difficulties adjusting behavior to suit various social M /90&99),-*+1)&0,//0N/)<,+01&0,//0, 0,&)&=3,+O M &1%,/:&1%,81&+1))18)&0&)&30 DSM-5 workgroup reasoning • “ASD” for Autism, Asperger Syndrome, CDD, PDD-NOS – – – – K NU]]XO+K KNVTTTO contexts – Stereotyped or repetitive motor movements, use of objects, or speech; – Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior; – Highly restricted, fixated interests that are abnormal in intensity or focus; – Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment; DSM-5 definition of ASD • Symptoms must be present in the early d e v e l o p m e n t a l p e r i o d (may not be fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life) • Symptoms cause clinical significant impairment in social, occupational, or other important area of current functioning; • Not better explained by intellectual developmental d i s o r d e r o r g l o b a l d e v e l o p m e n t a l d e l a y (discrepancy between social communication skills and intellectual ability) • If child/individual met DSM-IV criteria for autistic d i s o r d e r, A s p e r g e r ’ s , o r P D D - N O S ( w e l l - e s t a b l i s h e d ) , DSM-5 diagnosis of ASD applies; • If marked deficits in social communication, but does not meet criteria for ASD, evaluate for Social (Pragmatic) C o m m u n i c a t i o n D i s o r d e r (i.e., no symptoms in the 2nd domain) DSM-5 definition of Social (Pragmatic) Communication Disorder DSM-5 definition of ASD • Specify – if intellectual impairment – if language impairment – if associated with known medical or genetic condition or environmental factor (additional code) – if associated with another neurodevelopmental, mental, or behavior disorder – if catatonia (????!!!!!) • No more multi-axial system (of DSM-IV) • Severity Levels of ASD – Separate for Social Communication, and for Restricted, Repetitive Behaviors – Level 3: Requiring very substantial support – Level 2: Requiring substantial support – Level 3: Requiring support DSM-5 definition of Social (Pragmatic) Communication Disorder • Onset: early developmental period • Persistent difficulties in the social use of verbal and nonverbal communication: – Deficits in using communication for social purposes, such as greeting and sharing information appropriate to social context – Impairment of the ability to change communication to match context or the needs of the listener (such as speaking differently in, and adjusting to different contexts) – Difficulties following rules for conversation and storytelling (taking turns in conversation, rephrasing when misunderstood, using verbal and nonverbal signals to regulate interaction) – Difficulties understanding what is not explicitly stated (making inferences) and nonliteral or ambiguous meanings of language (metaphors, humors, irony) • Deficits result in functional limitations in effective communication, social relationships, academic achievement, or occupational performance (but deficits may not become fully manifest until social communication demands exceed limited capacities) • Symptoms not attributable to another medical or neurological condition, low abilities in word structure and grammar • Symptoms not better explained by ASD, intellectual d i s a b i l i t y, g l o b a l d e v e l o p m e n t a l d e l a y o r a n o t h e r m e n t a l d i s o r d e r. • “ R a r e < 4 y e a r s ” ; Va r i a b l e o u t c o m e • Risks: family history of ASD, communication disorders, s p e c i f i c l e a r n i n g d i s o r d e r. • Is this a back door to “Broader Autism Phenotype” (BAP) moved outside its original (ASD) familial context? • ASD without RRBs (current or by history!) • Other rule outs: ADHD, Social Phobia, ID Advocacy Groups’ position and concerns • Misdiagnosis or underdiagnosis of people with Asperger’s Disorder • “Asperger’s” has meaning to individuals affected, families, service providers, organizations, communities, the general public • Symptoms not comprehensive enough: Less Discussed Complexities • The dependency upon ADI-R and ADOS • – sensory atypicalities, anxieties, Executive Dysfunction, RH learning difficulties - important for treatment/educational programming • • Scales for measurement of ASD diagnostic criteria not released yet -> Indices of Severity • • – who administers these instruments – reliability at the item level – Doing away with the experienced clinician Where are the challenges most felt – Are these challenges captured by the instruments – The need for real-life instrumentation The “subthreshold” symptoms – A “milder” social disability – The real-life consequences of defining it as “mild” Self-representation The reality of community-based practices: the importance of DSM QUO VADIS “diagnostic process” and DSM-5 • All encompassing definition: need for quantification and individualization • Need for “tests” that are both diagnostic and prescriptive • Redefining autism/ASD for the biological sciences (NIMH) • What is “core” and what are “associated disabilities” • Could these associated disabilities be significantly attenuated if not prevented? Thank you Now you truly deserve to go to lunch ... Have a wonderful symposium! It will be terrific!